One of the major strategies utilized for the improvement of treatment and diagnosis of cancer is to increase the concentration of the anticancer drug in the cancer, by targeting the drug to the cancer, utilizing antibodies and antibody fragments specific to epitopes (antigens) on the cancer cells. This leads to increased therapeutic effect and reduced toxic effects by increasing the ratio of drug concentration in the cancer to the drug concentration in the rest of the body. This strategy is used for enhancing the visualization of the cancer by achieving an increased ratio of isotope concentration in the cancer to the isotope concentration in the rest of the body. Background radioactivity is reduced, cancer radioactivity is increased and cancer visualization is improved.
The methods utilizing direct radioactive labeling by isotopes of targeting antibodies with specific affinity to cancer epitopes are reviewed by C. Lollo et al (Nuclear Medicine Communications, Vol 15, pp 483–491, (1994) Lollo et al also describe an improved targeting method that utilizes hybrid F(ab′)2, obtained from two monoclonal antibodies, one with specific affinity to a radiolabeled hapten 111indium-nitrobenzyl-ethylene diamine tetraacetic acid (111In-NBE), and the other with specific affinity to a cancer antigen, carcino embryonic antigen (CEA). An added strategy to the ligand targeting method is utilization of the extracorporeal immunoadsorption methods of U.S. Pat. Nos. 4,834,973 and 4,620,977 to Strahilevitz. These patents disclose methods and devices for the specific removal of ligands from the blood circulatory system and body stores by extracorporeal immunoadsorption of the ligand. James L. Lear et al (Radiology, Vol 179, pp 509–12 (1991)) utilized the methods of the Strahilevitz patents in conjunction with targeting of a visualization ligand. Lear et al utilized a mouse monoclonal antibody with specific affinity to human milk fat globule membrane antigen, which is an epitope (antigen) expressed in many epithelial tumors, including human breast and non-small cell lung carcinomas. The antibody was conjugated with 1-(para-isothiocyanatobenzyl) diethylenetriamine-pentaacetic acid and the conjugate was radiolabeled with 111indium. The conjugate was removed from the circulation of the patients by extracorporeal immunoadsorption using as the adsorbent goat antimouse antibody. The addition of the extracorporeal immunoadsorption step was found to increase the ratio of radiolabel concentration in cancer to radiolabel concentration in the rest of the body, and to significantly improve the radiovisualization, when compared to the radiovisualization obtained by use of antibody-targeted radiolabel, without the additional step of extracorporeal immunoadsorption.